Modular Synthesis of Highly Substituted Benzenes from Divinyl Carbinols via a Pericyclic Cascade

Abstract Herein, we report a single step synthesis of highly substituted arenes from vinyl sulfoxide-tethered divinyl carbinols through a cascade sequence involving Claisen rearrangement, sulfoxide elimination, 6π-electrocyclization, and auto-oxidation. Simple variation of the reaction temperature allows the isolation of the proposed triene aldehyde intermediate. This method requires neither explosive reagents nor rare transition metals and proceeds without an inert atmosphere. Acyclic divinyl carbinol precursors are readily accessible by the addition of relevant nucleophiles to unsaturated aldehydes, enabling modular installation of up to four different substituents. The substituent pattern of the carbinol is directly transferred to the arene, enabling access to otherwise challenging aromatic substitution patterns. The resulting aldehyde functionality provides an additional synthetic handle, as demonstrated by the first total synthesis of Nigerapyrone B.